The objectives of this proposed research are to understand the mechanisms whereby pulmonary vascular smooth muscle produces persistent pulmonary hypertension in the hypoxic experimental animal, which may in turn lead to further understanding of some human pulmonary hypertensive disease. The methods to be used include standardization of the hypoxic pulmonary hyperterative rat as a model of human disease and to relate the various phases of pulmonary arteriolar wall changes to the simulated pulmonary hypertensive disease process. Changes in the arteriole will be examined by histological, histochemical and electron microscopic methods.